Retrograde tracers injected into the mouse brain backfill the cell bodies of their input projections
and
fluoresce,
as shown here. A combination of classical tracing techniques combined with novel rabies methods
allows for
the
systematic elucidation of specific neuronal circuits, anatomy, and morphology. By injecting several
different
tracers
into a single subject, the projections from the cortex can be shown with precise spatial relativity,
further
enriching
the data that can be captured from each subject.

Regulatory elements controlling gene expression can be detected by identification of regions of open
chromatin (scATAC-seq),
or changes in the level of cytosine methylation (scmC-seq) in the genomes of single cells. Applying
these
complimentary
state-of-the-art DNA sequencing techniques to record the pattern in individual brain cell nuclei
generates an
epigenetic
fingerprint for each cell. These fingerprints can be used to classify unique cell types and, when
linked to
specific
neuronal circuits across brain regions, lead to the discovery of new genetic determinants of
neuronal cell
function.

Sparse GFP labeling in the cortex of a two-year old marmoset (Callithrix jacchus). This marmoset was
injected with
AAV2.9hSyn1-GFP-p2a-GFPf with an incubation period of 56 days. After perfusion, the slices were
stained with
Alexa-488
Anti-GFP and imaged at 4x.

Photo primary slice culture tissue stained to show fiber architecture (green), progenitor cells
(red), and
neurons
(blue). Understanding human brain development is crucial to understanding stem cell function, how
neurons and
glia
are made, and as a foundation for potential regeneration medicine therapies. The structure of a
cortical
brain
slice, shown here, shows a sliver of the dynamic cell types, behaviors, and organization that
emerges during
brain
development.

Whole brain morphology reconstruction demonstrating multiple cell types in the isocortex. Two
distinct cell
types
were identified based on their whole brain projection patterns. One type has projections restricted
to
ipsilateral
cortex, while the other type sends projections to the homotypic region of the contralateral
cortex.

Example of transfer of information from micron-scale imaging
to in vivo studies. Five cortical areas were manually labeled in the
OCT AIP image (1), then registered to ex vivo MRI of the
hemisphere that it was taken from (2). The areas were sampled
onto an ex vivo surface model for that subject (3). Surface-based
registration is then used to map these labels to models derived
from in vivo ADNI subjects (4). This approach, when enabled by
our proposed technology, will allow us and others to carry out
morphometry studies in these predicted regions (5) revealing
disease effects on laminar structure, cell density and myelin content.

Single-cell analyses to resolve cellular diversity in the adult human brain. Brain tissues are imaged
and spatially registered using MRI, and sampling regions (visual cortex or BA17) are processed for
single cell assays. Gene expression and chromatin accessible site mapping permits unbiased
clustering of nuclei (visualized using t-SNE) and cell type annotation. Integration of these
expression and regulation profiles provides more detailed molecular annotation of the cell types
that can then be spatially mapped to the brain tissue sections using DART-FISH.

NIH's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative - Cell Census Network (BICCN) aims to provide researchers and the public with a comprehensive reference of the diverse cell types in human, mouse, and marmoset brain. A network of integrated centers and laboratories including U01, U19 data centers, R24 data archives, and a U24 Brain Cell Data Center (BCDC) are working collaboratively to share these data with the community. This site is the entry portal to the data, tools, and knowledge for this program.

Data, Tools, and Knowledge for Cell Types

A goal of the Brain Cell Data Center (BCDC) is to make all regularly released data available to the public. R24 Archives for transcriptomic based and image based data provide the archival storage and access for these data. As computational and visualization tools for these data are developed they will be released and linked here. As our knowledge of the relationship of these data modalities is uncovered, cell type summary knowledge will be presented to help enhance of our understanding of the role of cell types in the brain.

For further information about the BICCN please write to info@biccn.org.